ABSTRACT
Two tyrosine derivatives, dopamine and 4-hydroxyphenylacetaldehyde (4-HPAA), are formed from tyrosine via tyramine and 4-hydroxyphenylpyruvate (4-HPP), respectively. Decarboxylation of tyrosine to tyramine and transamination of tyrosine to 4-HPP are catalyzed by tyrosine decarboxylase (TYDC) (Facchini and De Luca 1994) and tyrosine aminotransferase (TyrAT) (Lee and Facchini 2011), respectively. (S)-Norcoclaurine is generated through the Pictet-Spengler condensation of 4-HPAA and dopamine catalyzed by norcoclaurine synthase (NCS). NCS is a protein of the pathogenesis-related 10 (PR10) and Bet v 1 allergen protein family in opium poppies and T. flavum (Lee and Facchini 2010; Liscombe et al. 2005; Samanani et al. 2004). Coptis japonica has two types of NCS, PR10-type CjPR10A and CjCNS, a protein with a similarity to 2-oxoglutarate-dependent dioxygenase (ODD) but lacking a conserved 2-oxoglutarate-binding motif (Lee and Facchini 2010; Minami et al. 2007). (S)-Norcoclaurine is converted to (S)-reticuline through a series of modications catalyzed by norcoclaurine 6-O-methyltransferase (6OMT) (Facchini and Park 2003;
Figure 5.1 Biosynthetic pathways for benzylisoquinoline alkaloids. Enzymes for which cDNAs have been cloned are shown in bold. (Abbreviations: TYDC, tyrosine decarboxylase; TyrAT, tyrosine aminotransferase; 4-HPP, 4-hydroxyphenylpyruvate; 4-HPAA, 4-hydroxyphenylacetaldehyde; NCS, norcoclaurine synthase; 6OMT, norcoclaurine 6-O-methyltransferase; CNMT, coclaurine N-methyltransferase; NMCH, N-methylcoclaurine 3′-hydroxylase; 4′OMT, 3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase; STORR, (S)- to (R)-reticuline; SalS, salutaridine synthase; SalR, salutaridine reductase; SalAT, salutaridine 7-O-acetyltransferase; CODM, codeine O-demethylase; T6ODM, thebaine 6-O-demethylase; COR, codeinone reductase; BBE, berberine bridge enzyme; CFS, cheilanthifoline synthase; SPS, stylopine synthase; TNMT, tetrahydroprotoberberine cis-N-methyltransferase; MSH, (S)-cis-N-methylstylopine 14-hydroxylase; P6H, protopine 6-hydroxylase; DBOX, dihydrobenzophenanthridine oxidase; SanR, sanguinarine reductase; SOMT, scoulerine 9-O-methyltranfease; CAS, canadine synthase; STOX, (S)-tetrahydroberberine oxidase; AT1, acetyltransferase1; CXE1, carboxyesterase1; NOS, noscapine synthase.) (Continued)
Figure 5.1 (Continued) Biosynthetic pathways for benzylisoquinoline alkaloids. Enzymes for which cDNAs have been cloned are shown in bold. (Abbreviations: TYDC, tyrosine decarboxylase; TyrAT, tyrosine aminotransferase; 4-HPP, 4-hydroxyphenylpyruvate; 4-HPAA, 4-hydroxyphenylacetaldehyde; NCS, norcoclaurine synthase; 6OMT, norcoclaurine 6-O-methyltransferase; CNMT, coclaurine N-methyltransferase; NMCH, N-methylcoclaurine 3′-hydroxylase; 4′OMT, 3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase; STORR, (S)- to (R)-reticuline; SalS, salutaridine synthase; SalR, salutaridine reductase; SalAT, salutaridine 7-O-acetyltransferase; CODM, codeine O-demethylase; T6ODM, thebaine 6-O-demethylase; COR, codeinone reductase; BBE, berberine bridge
Morishige et al. 2000; Ounaroon et al. 2003), coclaurine N-methyltransferase (CNMT) (Choi et al. 2002; Facchini and Park 2003), CYP80B subfamily N-methylcoclaurine 3′-hydroxylase (NMCH) (Haung and Kutchan 2000; Ikezawa et al. 2003; Pauli and Kutchan 1998), and 3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase (4′OMT) (Facchini and Park 2003; Morishige et al. 2000; Ziegler et al. 2005). (S)-Reticuline serves as a central intermediate among pathways leading to different structural subgroups of BIAs, as some BIAs such as papaverine are synthesized via upstream intermediates of reticuline (Desgagné-Penix and Facchini 2012; Pathak et al. 2013).
